As the computational methods used in pharmaceutical development improve, receptor binding analysis has led to many potential new drug candidates that are polycyclic. Such leads are often not pursued, however, because of the perception that even if the compound were active, an enantiomerically pure polycyclic candidate would be too expensive to manufacture. An investigation of a new method for the construction of carbocyclic rings, intramolecular alkylidene C-H insertion, is proposed. One could take nearly any complex cyclic molecule and do a retrosynthetic disconnection in such a way as to generate an alkylidene carbene precursor. Tetrodotoxin, N-deacetyllappaconitine and sordaricin have been selected as targets because of their structural interest and their pharmacological significance. In the course of these investigations, new molecular reactivity will be developed that will substantially shorten current routes to polycyclic natural products and drug candidates.